RESUMO
Ionizing radiation is a widely used therapy for solid tumors. However, high-dose ionizing radiation causes apoptosis, transforms normal cells into tumor cells, and impairs immune functions, leading to the defects in the removal of damaged or tumor cells. In contrast, low-dose radiation has been reported to exert various beneficial effects in cells. This experimental study investigated the effect of γ rays at low dose on the development of colorectal tumor in a 1,2-dimethylhydrazine (DMH)-induced colon cancer. Colorectal tumor model was induced in Wistar rats by subcutaneous injection of DMH (20 mg/kg) once a week for 15 weeks. Starting from zero day of DMH injection, a single low dose of whole-body γ irradiation of 0.5 Gy/week was applied to the rats. A significant reduction in lipid peroxidation, nitric oxide, and elevation in the glutathione content and antioxidant enzyme activity (superoxide dismutase and catalase) were observed after γ irradiation comparing with DMH group. Moreover, γ ray reduced the expressions of multidrug resistance 1 (MDR1), ß-catenin, and cytokeratin 20 (CK20) those increased in DMH-treated rats. However, survivin did not change with γ ray treatment. A histopathological examination of the DMH-injected rats revealed ulcerative colitis, dysplasia, anaplasia, and hyperchromasia. An improvement in the histopathological picture was seen in the colon of rats exposed to γ rays. In conclusion, the present results showed that low-dose γ ray significantly inhibited DMH-induced colon carcinogenesis in rats by modulating CK20, MDR1, and ß-catenin expression but not survivin expression.
Assuntos
Colite Ulcerativa/radioterapia , Neoplasias do Colo/radioterapia , Raios gama/uso terapêutico , 1,2-Dimetilidrazina , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Carcinógenos , Catalase/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Glutationa/metabolismo , Queratina-20/genética , Queratina-20/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Óxido Nítrico/metabolismo , Ratos Wistar , Superóxido Dismutase/metabolismo , beta Catenina/genéticaRESUMO
The protective role of soybean feeding against the cytogenetic and histopathologic effects of the nitrosamine precursors sodium nitrate and dibutylamine was evaluated. Treated animals were killed every 3 months, over a period of 15 months, and bone marrow cells were prepared for cytogenetic studies and livers for histopathological observations. Structural chromosomal aberrations and mitotic indices increased after treatment with the nitrosamine precursors for all tested times. Livers were within the normal appearance during the first 6 months. After that a mild, moderate, marked dysplasia with lymphocytic infiltration, fatty vacuolation and liver atrophy was observed. Soybean coadministered with the nitrosamine precursors reduced the number of structural chromosomal aberrations. Mitotic indices decreased at all tested groups but still higher than the control level. A marked reduction in dysplastic features in the liver cells was observed. In conclusion, the cytogenetic and histopathologic results of this study strongly support the protective role of soybean against the genotoxic and carcinogenic action of nitrosomine formed in vivo from its precursors.